Steroidal azines



iinited States Patent 6 The object of this invention is the preparationof compounds that can be represented by the following general formula:

wherein R and R are members selected from the group consisting of H andCH while R" isa member selected from the group consisting of H and analiphatic acyl radical containing from 2 to 10 C atoms. These compoundsare very useful as anabolic agents because of their favorableanabolic-androgenic ratio and because of the nitrogen retention theyafiord. They are prepared from the corresponding S-hydrazones that aredescribed in the pending application Serial No. 145,481, filed October16, 1961, either by dissolving them in one of several solvents andallowing the solution to stand, or by a heat-treatment. It is Well knownto the organic chemist that hydrazones are thus converted into azines.Obviously, other method which are commonly followed for the preparationof azines can be employed as well. Such methods are for instance thereaction between 2 moles of a ketone and 1 mole of hydrazine hydrate, orthe reaction between 1 mole of a hydrazone and 1 mole of a ketone.However, dissolving the hydrazone in chloroform or in another solventand allowing this solution to stand for a While is an easier method, andit is therefore to be preferred.

The 175 acyl derivatives can be prepared directly from S-hydrazones thathave been previously acylated in their 17 position, or from the azines,through acylation with the usual methods.

The following examples are given only for the purpose of furtherillustrating our invention, and they are not to be construed as limitingthe scope of the present invention in any way:

EXAMPLE NO. 1

ZwMethy l-a-Andr0stane-1 7fl-0l-3-0ne-Azin'e 0.7 part of2a-methyl-5a-androstane-17,6-ol-3-hydrazone is refluxed for 3 hours with0.3 part of Za-methyi-Suandrostane-l7/3-ol-3-one dissolved in parts ofabsolute alcohol. After evaporation to dryness, the product isrecrystallized from methanol. The yield is 0.65 part of 2c: methyl 50candrostane-l7B-ol-3-one-azine, having M.P.=238239 C. and (a) =+129(chloroform).

.EXAMPLE NO. 2

2a,] 7u-Dimethyl-5 a -AndrQstan e -1 7 8-ol-3-0ne-Agine 2 parts of 20,17a-dimethyleiaeandrostane- 175-01-34 rdrazoiie are. dissolved; in 10parts of chloroformv and the solution is kept at room "temperature for-24 hours. Itlis then evaporated to drynessand ,the produc t lislrecrlystallized from methanol. Theyield is 1.95 partsof 205,17dimethyl-Sa-androstane-l7B-o1-3-azine, having M.P.= 265-26,7 C. and (a).=:+ll6 (chloroform).

EXAMPLE No.3 Za-MethyI-Sa-Estrane-I 7501-3 -0ne-Azine 5.8 parts of2a-methyl-5a estrane-17flFol-3-one, dissolved in 58.partsof ethanol, arerefluxed for 3 hours with 0.65 part of hydrazine hydrate. YAfter partialevaporation, water is added, and the product is collected by filtration.It is then recrystallized from methanol. The yield is 4.2 parts of2u-methyl-5a-estrane-17fi-ol-3-azine, having M.P.=234-236 C. and (u)=|ll2 (chloroform).

EXAMPLE NO. 4

2a,] 7ot-Dimethy l-5 -Estra1ne-1 Z pol-3 One-1i zine 2 parts of2a,17a-dimethyl-5 x-estrane-17p-ol-3ehydrazone are refluxed for 3 hourswith 10 partsof ethyl acetate. After evaporation to dryness, the productis recrystallized from methanol. The yield is 1.95 parts of 201,170L d1-methyl-ia-estrane-17fl-ol-3-one-azine, having M.P.=242243 C.

and (oc) =+1Q(l (chloroform).

EXAMPLE NO. 5

ZOL-M ethyl-1 7 p-Acetoxy -5 a-A ndrostaned-On'eeAzine 2 parts ofZa-rnethyl-17 8-acetoxy-5a-androstane 3-hydrazone are dissolved in 10parts of chloroform and the solution is allowed to stand for 24 hours.It is then evaporated to dryness and the product is recrystallized frommethanol. The yield is 1.9 parts of 2u-methyl-17B-acetoxy-5a-androstane-3-one-azine, having M.P.=267269 C.

and (a) (chloroform).

EXAMPLE NO. 6

2a-Methyl-Jiot-Androstane-l 7fi-Pr0pi0nyloxy-3-One- Azine 3 parts ofpropionic anhydride are added to 1 part of2ot-methyl-5a-androstane-17fi-ol-3-azine dissolved in 6 parts ofpyridine. After standing for 12 hours at room temperature, water isadded and the product is collected by filtration and recrystallized frommethanol. The yield is 1.05 parts ofZu-methyl-Sa-androstane-l7fi-propionyloxy-3-one-azine, havingM.P.=249-251 C. and

(a) +124 (chloroform).

EXAMPLE NO. 7

20L-Methyl-50L-A ndrostane-I 7B-Hexanoyl0xy-3-One- Azine 0.8 part of2u-methyl-5u-androstane-l7B-hexanoyloxy- 3-hydrazone is refluxed for 4hours with chloroform. After evaporation to dryness, the product isrecrystallized from methanol. The yield is 0.65 part ofZa-methyI-Saandrostane-17/3-hexanoyloxy-3-one-azine, having M.P.=240242C.

and (a) =+l14 (chloroform).

evaporated to dryness.

EXAMPLE No. 8

Zw-M ethyl-1 7 [3-H eptanoy loxy-S oc-A ndrstane-3 -O n e Azine 2 partsof 2u-methyl-5a-androstane-17fi-ol-3-one-azine dissolved in 4 parts ofpyridine are refluxed for 2 hours with 2 parts of enanthic anhydride.Water is then added and the solvent'is steam distilled. The product isextracted with chloroform, and the chloroform solution is The product isthen recrystallized from methanol. The yield is 2.1 parts of2a-methyl-17flheptanoyloxy 5a androstane 3 one azine, having M.P.=206208C. and (a) =+112 (chloroform).

EXAMPLE NO. 9

2u-Methyl-Sa-Andmstane-l 718-D ecan0yl0xy-3-One-A zine 2 parts ofZa-methyl-Sa-andmstane-17,8-decanoyloxy-3- hydrazone are refluxed for 6hours with 5 parts of absolute alcohol. After evaporation to dryness,the product is recrystallized from methanol. The yield is 1.75 parts of2m methyl-Sa-androstane-17fi-decanoyloxy-3-one-azine, having M.P.=l94196C. and (a) =+140 (chloroform).

EXAMPLE NO. 10

Za-Methyl-Sa-Estrane-l 7fl-Pr0pionyl0xy-3-One-A zine 1 parts ofZa-methyI-Sa-estrane-175-01-3-one-azine dissolved in 3 parts of pyridineis added with 1.5 parts of propionic anhydride. After standing overnightat room temperature, water is added and the product is collected byfiltration. It is then recrystallised from methanol. The yield is 1.05parts of Za-methyI-Su-estrane-I7a-propionyloxy-3-one-azine, havingM.P.=24l-243 C. and (u) =+-100 (chloroform).

EXAMPLE NO. 11

2 a-Methyl-Sa-Estrane-l 7B-Heptan0yl0xy-3-One-A zine 0.6 part ofZa-methyl-Sa-estrane-17fi-heptauoyloxy-3- hydrazone is dissolved in 20parts of chloroform and kept for 12 hours at room temperature.

After evaporation to dryness, the product is recrystallized frommethanol. The yield is 0.52 part of 2a-methyl- 4-Sa-estrane-l7fl-heptanoyloxy-3-one-azine, having M.P.= 247-250 C. and(a) =l-120 (chloroform) I claim: 1. A compound of the formula: 5 on" R 1H 6 H 111- z wherein R and R are members selected from the groupconsisting of H and CH and R" is a member selected from the groupconsisting of H and an aliphatic acyl radical containing from 2 to 10 Catoms.

Zu-methyl-Sa-androstaue-17/3-ol-3-one-azine.2a-17u-dimethyl-5a-androstane-17fi-ol-3-one-azine.Za-methyI-Sa-estranc-17fi-0l-3-one azine. 2a,l7a-dimethyl-5c4-estrane-l7B-ol-3-one-azine.2m-methyl-17,8-acetoxy-5a-androstane-S-one-azine. 2amethyl-17fi-propionyloxy-5a-androstane-3-oneazine.

8. 2oz methyl 17B-hexanoyloxy-5u-androstane-3-oneazine.

9. 2a methyl-17B-heptanoyloxy-Sa-androstane-B-oneazine.

10. 2a methyl l7 9-decanoyloxy-5u-androstaue-3-oneazine.

11. 2oz methyl 175-propionyloxy-Sa-estrane-S-oneazine.

12. 2a methyl l7fl-heptanoyloxy 5a estrane-3-oneazine.

No references cited.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No 062,847November 6, 1962 Pietro de Ruggieri It is hereby certified that errorappears in the above numbered patent requiring correction and that thesaid Letters Patent should read as corrected below.

Column l lines 14 to SC and column 4, lines 5 to 21, th lower left-handportion of the formula, each occurrence, should appear as shown belowinstead of as in the patent:

Signed and sealed this 3rd day of September 1963,

(SEAL) Attest:

ERNEST w. SWIDER DAVID LADD Attesting Officer Commissioner of Patents

1. A COMPOUND OF THE FORMULA: